Elaborate chemistry tools applied to peptides and proteins have led to unparalleled structure-function studies and tailor-made bio-therapeutics. Yet, given inherent limitations of existing methods new chemical tools are needed for routine modification and engineering of biomolecules. Specifically, at the peptide level, areas of recent advancement include the use of macrocyclization chemistry to constrain these species via hydrocarbon linkers, aromatic clips, or lactam bridges. These modifications have generated excitement in the field of peptide therapeutics because in some cases the introduced constraint has led to peptides capable of penetrating cells thereby making a wide range of intracellular proteins and interactions targetable by these variants. Recent examples for chemistry applied to the creation of protein therapeutics involve the use of total protein synthesis to prepare mirror image proteins that target VEGF, the incorporation of non-natural amino acids for site-specific attachment of PEG-like polymers to protein drugs, and the small molecule antibody therapeutic conjugates. Currently, significant efforts are underway to design peptides and proteins as inhibitors of medically relevant protein-protein interactions; these molecules are being widely developed because they display a large surface area that can bind and recognize a target with high affinity and specificity. The chemical modification of unprotected peptides and proteins has proved challenging because one-site often needs to be labeled or modified in the presence of many other functional groups. Consequently, the reactions employed need to be chemoselective, regioselective, and operational under mild, biomolecule friendly conditions. Here we propose to develop cysteine arylation as an extensive tool for bioconjugation and to decipher how these perfluoroaryl groups affect the structure and function of a select class of bioactive peptides and proteins. We aim to investigate cysteine arylation with a variety of perfluoroaromatic reagents, to develop enzyme-catalyzed version of the chemistry, and to carry out structure-function studies on bioactive proteins and peptides containing these perfluoroaryl moieties. In our opinion, the research proposed here will make fundamental and practical contributions to the field of chemical biology by introducing a new method to modify peptides and proteins, and will impact the area of next-generation bio-therapeutics.